Strabismus, the misalignment of the eyes, is prevalent in the US and usually treated surgically with imperfect results. This is the predictable result of an inadequate paradigm for understanding orbital anatomy and the biomechanics of binocular alignment, sometimes leading to erroneous diagnoses and surgery. The overall aim of this project is to develop a physiologically realistic, quantitative understanding of the biomechanics of the extraocular muscles (EOMS) and associated connective tissues responsible for the movement and alignment of the eyes, and to apply this information to the diagnosis and treatment of strabismus. Recent evidence in humans and other primates shows that orbital connective tissues form a complex gimbal system to regulate ocular kinematics. The global layer of each rectus extraocular muscle (EOM) rotates the eye, while the orbital layer of that EOM translates the connective tissue pulley that serves as the EOM's functional origin. Pulleys play a crucial role in normal biomechanical alignment. Congenital and acquired abnormalities of pulleys cause some types of pattern strabismus, and others may be related to manipulations of pulley tissues during strabismus surgery. We propose a multidisciplinary approach to understanding the mechanics of binocular alignment through parallel studies in humans and monkeys. We will employ magnetic resonance imaging (MRI) to obtain near-microscopic resolution of EOMs and connective tissues as they change with the direction of gaze in normal and strabismic subjects. We will test "the active pulley hypothesis" that the dynamic translational position of normal pulleys is regulated to be consistent with ocular kinematic behavior such as Listing's Law of ocular torsion. We will study EOM pulleys in normal aging, where characteristic forms of strabismus become prevalent. Comparison of orbital imaging in congenital and acquired cyclovertical strabismus will provide evidence concerning the causal relationship between pulley heterotopy and strabismus. We will investigate the possible relationship between pulley abnormalities and two common co-morbidities of esotropia, dissociated vertical deviation and inferior oblique overaction. We will investigate in humans the effects of aging and other pathology on EOM connective tissue structure and constituents, and behaviorally and anatomically define the relationship of EOM proprioceptive organs to pulleys. We will compare pulleys in normal monkeys with those who are naturally and artificially strabismic. Data will be tested in computational models of binocular alignment suitable for clinical use. Findings will critically evaluate a new and potentially more useful paradigm for the understanding of ocular motility and treatment of strabismus.